We presented a case of new onset cryptogenic stroke in an elderly patient with finally diagnosed isolated PAVF. Initially, the thrombus in the M2 segment of the left cerebral artery in this patient was thought to originate from stenosis of the ipsilateral carotid artery. Arterial-to-arterial embolism would be the primary consideration in terms of etiology. Given the patient's age, carotid artery stenosis is often associated with atherosclerosis. However, this patient lacked conventional arterial sclerosis risk factors, and after intravenous thrombolysis treatment, both the cerebral artery and the carotid artery were completely patent, suggesting that carotid artery stenosis was not true stenosis but rather thrombi in nature. Following a series of examinations during hospitalization, we identified paradoxical embolism in the patient. There was a PAVF in the lungs, and deep vein thrombosis was present in the lower limbs. Therefore, we ultimately considered that the cause of the stroke in this patient was PAVF.
PAVF is a rare vascular anomaly characterized by an abnormal connection between the pulmonary artery and vein without capillaries in the lungs (2), leading to various degrees of right-to-left shunt. A 2012 analysis of data gathered using thoracic CT scanning show a prevalence rate of 38/100,000 and its incidence is twice as common in women(3). Incidence of stroke has been reported range 9.3–70% in the PAVF patients with HTT, while this cannot be report in isolated PAVF patients.(4, 5) In particular, PAVF is an important cause of stroke in young adult (6). Another retrospectively study showed that the ratio of PAVF among AIS was 0.02% and the mean age was 57.5 years (7). In other word, the initial diagnosis of PAVF is even rarer in elderly stroke patients.
PAVF-related ischemic strokes may be cortical or subcortical, but very rarely cause proximal large vessel occlusions. Only one of the case reports described a proximal (M1– middle cerebral artery) large vessel occlusion(8), and another reported a right M2-MCA occlusion(9). Besides, a case report described a PAVF mimicking vertebral artery dissection(10). In this case, both CCA and M2-MCA had thrombi, and was thought to be arterial-to-arterial embolism at first. So, PAVF-related proximal large vessel occlusion may not rare, but not detected.
At present, authoritative clinical practice guidelines of Intravenous thrombolytic therapy for PAVF-related paradoxical cerebral embolism are generally lacking. According to the British Thoracic Society Clinical Statement, but the safety of thrombolysis and clinical benefit is not established (2). Moreover, no cohort studies or case series to date have described use of Intravenous thrombolytics in AIS patients with PAVF. Only a handful of case reports described the use of thrombolytics(6). In the 2005–2014 NIS study (7), patients with and without PAVF received intravenous thrombolytics at a similar rate (5.9% versus 5.8%), but they didn’t compare the bleeding complications. In general, the potential for bleeding complications in PAVF is an issue with thrombolytic therapy, the high risk of fatal pulmonary bleeding, epistaxis and gastrointestinal bleeding from comorbid telangiectasia, especially in cases of HHT (11). However, PAVF often had not been diagnosed until patients presented an ischemic stroke (6), thus it is not easy to diagnose PAVF at the time of stroke onset in real world. In our case, the patient received intravenous thrombolysis achieved a really good outcome without any bleeding complications. So, thrombolytic therapy might be a choice for patients with isolated PAVF within a time window.
For secondary prevention of stroke, no clear statement for optimal antithrombotic management for cerebral embolism due to PAVF. In a recent study of 4271910 AIS patients with 822 diagnosed with PAVF, patients with PAVF were ≈ 2-fold more likely to be on long-term anticoagulation after adjusted for multiple confounders(7). The most recent international guidelines for HHT management recommend that, when indicated, preventive antithrombotic regimens consist of either single antiplatelet or anticoagulant therapy, avoiding double antiplatelet therapy or combined antiplatelet and anticoagulant therapy(12). While, the second stroke prophylactic measure for ischemic strokes caused by large artery atherosclerosis is double antiplatelet therapy. In our case, the patient combined with deep venous thrombosis on lower extremity ultrasound, we selected Rivaroxaban as secondary prevention strategy with on recurrence before embolization therapy.
Endovascular embolization therapy is the preferred treatment for PAVF (1, 11). PAVF treatment reduces risks from paradoxical emboli and symptoms exacerbated by right-to-left shunting and haemorrhage(2). Embolisation is a safe intervention in experienced hands(2). In the former, embolisation is indicated, If one of the following criteria is met: any (solitary or multiple) PAVF with a feeding artery with diameter of 2 mm or larger, measurable increase in size of PAVF, and paradoxical emboli or symptomatic hypoxemia. However, currently, embolization is recommended for all treatable PAVs regardless of feeding artery size, even for asymptomatic patients (1).